This study will use the genetic linkage between the HLA region and susceptibility to juvenile-onset, insulin-dependent diabetes mellitus (JOD) to determine the mode of inheritance of susceptibility to the disease. We will also characterize further the HLA specificities associated with JOD by mixed lymphocyte culture with cells from appropriate diabetics and their relatives. Family studies in kindreds with two or more maturity-onset type diabetic (MOD) sibs will allow us to determine whether, despite failures to find association in population studies, susceptibility to MOD is genetically linked to HLA. The methods of pedigree analysis will be used in a novel way with the data on JOD'S to incorporate information on segregation of HLA haplotype directly into the study of mode of inheritance. Testable genetic inferences will result; for example, "one allele at an autosomal locus is sufficient for susceptibility". Since susceptibility may be manifested in the phenotype of unaffected relatives, the genetic inferences will be tested by comparing the phenotype of unaffected sibs (and parents) who are at risk, given the genetic hypothesis, with that of comparable relatives not at risk.